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Biomedical subjects

O Chan

Publications and source records attributed to O Chan.

At least 19 recordsLinked to original sources

Jumpers and fallers: a comparison of the distribution of skeletal injury.

AIM: The aim of this study was to compare the distribution of injuries between patients who have fallen and those who have jumped from a height, and to relate the mechanism of injury to the fractures sustained. MATERIALS AND METHODS: Three hundred and ninety-nine patients, admitted via Helicopter Emergency Medical Service (HEMS), classified as either having fallen or jumped from a height were included in the study. The radiographs from the primary survey, together with radiographs of specific injury sites were analysed. The distribution of injury was compared in the two groups. RESULTS: Of the 399 patients, 342 were fallers and 57 were jumpers. Jumpers had a higher Injury Severity Score (ISS), death rate and number of fractures per person. Jumpers sustained more rib fractures (particularly on the right), pelvic and lower limb fractures but fewer skull fractures. CONCLUSION: Jumpers tend to sustain different injuries to fallers. It is proposed that jumpers have a tendency to land feet-first and then try to break their falls on their dominant side, sustaining more right-sided rib fractures in the process. The patterns of injury that have emerged from this study have important implications for evaluating skeletal injuries in those who jump or fall from a height.

Accidental Falls↗

Complications with use of the Epistat in the arrest of midfacial haemorrhage.

Control of midfacial haemorrhage can be difficult, especially in the multiply injured patient, either at the scene of injury, or in the Accident and Emergency Department. The use of Epistats has proven invaluable in this setting. Potential problems exist with their use and this is illustrated with examples, together with strategies for overcoming them. A summary of the didactic method of safe use of this life saving technique is insert the Epistat, aiming for a fingertip placed at the soft palate;inflate the posterior cuff;withdraw the Epistat slightly, to position the posterior cuff within the nasal choanae;inflate the anterior (intranasal) cuff.

Adolescent↗

Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis.

Patients and animals with poorly controlled or uncontrolled diabetes present with diurnal hypersecretion of glucocorticoids and altered regulation of the hypothalamo-pituitary-adrenocortical (HPA) axis. Although some of these changes are reversed with insulin replacement therapy, neuroendocrine function is not always restored to normal, even with rigorous glycemic control. In addition, stress responsiveness is also impaired in diabetes and this has important implications in the way patients with diabetes cope with many stress challenges, including the metabolic challenge of insulin-induced hypoglycemia. HPA dysregulation in diabetes appears to involve complex interactions between impaired glucocorticoid negative feedback sensitivity and factors such as hypoinsulinemia, hyperglycemia and/or hypoleptinemia, that may increase central drive of the axis. This review examines some of the evidence indicating hyperactivation of the HPA axis in patients with diabetes. Using the streptozotocin-diabetic rat as a model of type-1 diabetes, we will focus on elucidating some of the mechanisms underlying HPA dysregulation in diabetes. Hyperactivation of the HPA axis in diabetes is associated with increased expression of hypothalamic corticotrophin-releasing hormone (CRH) mRNA and hippocampal mineralocorticoid receptor (MR) mRNA. Although insulin replacement restores ACTH and corticosterone levels to normal, likely through glucocorticoid-mediated suppression of ACTH secretion, CRH and MR mRNA expression remain elevated. A better understanding of these mechanisms may be important in developing new treatment modalities for patients with diabetes mellitus.

Diabetes Mellitus↗

Mechanisms of impaired hypothalamic-pituitary-adrenal (HPA) function in diabetes: reduced counterregulatory responsiveness to hypoglycaemia.

In summary, our data suggest that in uncontrolled diabetes, increased HPA activity is caused by increased central drive at or above the level of the PVN. Insulin treatment only restores HPA activity at and below the pituitary level, presumably by GC-mediated suppression of ACTH secretion. We hypothesize that the defective HPA response to hypoglycaemia is at least in part due to a lack of a decrease in MR mRNA in response to hypoglycaemia, and diminished sensitivity of the pituitary and adrenal gland to stimulation. Interestingly, insulin treatment restores the HPA response, but not the defective epinephrine response. Therefore, defective epinephrine responses are not linked to defective HPA responses. Similarly, antecedent hypoglycaemia specifically impairs epinephrine responses, but not HPA responses to hypoglycaemia. These studies have revealed some of the mechanisms of impaired HPA function in diabetes and its impaired responsiveness to hypoglycaemia. Further investigations are essential for understanding poor counterregulation in insulin-treated diabetes and may lead to new strategies for preventing hypoglycaemia.

Adrenocorticotropic Hormone↗

Effects of antecedent hypoglycemia, hyperinsulinemia, and excess corticosterone on hypoglycemic counterregulation.

This study aimed to differentiate the effects of repeated antecedent hypoglycemia, antecedent marked hyperinsulinemia, and antecedent increases in corticosterone on counterregulation to subsequent hypoglycemia in normal rats. Specifically, we examined whether exposure to hyperinsulinemia or elevated corticosterone per se could impair subsequent counterregulation. Four groups of male Sprague-Dawley rats were used: 1) normal controls (N) had 4 days of sham antecedent treatment; 2) an antecedent hypoglycemia group (AH) had 7 episodes of hyperinsulinemic hypoglycemia over 4 days; 3) an antecedent hyperinsulinemia group (AE) had 7 episodes of hyperinsulinemic euglycemia; and 4) an antecedent corticosterone group (AC) had 7 episodes of intravenous corticosterone to simulate the hypoglycemic corticosterone levels in AH rats. On day 5, hyperinsulinemic euglycemic-hypoglycemic clamps were performed. Epinephrine responses to hypoglycemia were impaired (P < 0.05 vs. N) after antecedent hypoglycemia and hyperinsulinemia. This correlated with diminished (P < 0.05 vs. N) absolute glucose production responses in AH rats and diminished incremental glucose production responses in AE rats. Paradoxically, norepinephrine responses were increased (P < 0.05 vs. N) after antecedent hypoglycemia. Glucagon and corticosterone responses were unaffected by antecedent hypoglycemia and hyperinsulinemia. In AC rats, incremental but not absolute glucose production responses were decreased (P < 0.05 vs. N). However, neuroendocrine counterregulation was unaltered. We conclude that both antecedent hypoglycemia and hyperinsulinemia impair epinephrine and glucose production responses to subsequent hypoglycemia, suggesting that severe recurrent hyperinsulinemia may contribute to the development of hypoglycemia-associated autonomic failure.

Animals↗

Molecular regulation of the hypothalamo-pituitary-adrenal axis in streptozotocin-induced diabetes: effects of insulin treatment.

Increased hypothalamo-pituitary-adrenocortical (HPA) activity in diabetes is likely important in the development of some pathologies associated with the disorder. We hypothesized that central regulation of HPA activity differs among normal, streptozotocin (STZ)-diabetic, and insulin-treated diabetic rats. Blood glucose, ACTH, and corticosterone were elevated, 8 d after inducing diabetes. Insulin treatment normalized these parameters. Plasma norepinephrine was similar in all groups, but epinephrine was lower in STZ-diabetic and higher in insulin-treated rats vs. normals. Increased ACTH with diabetes corresponded with increased hypothalamic CRH mRNA, but no change in pituitary POMC mRNA. With insulin-treatment, CRH mRNA remained elevated, and POMC mRNA was unaltered. Hippocampal MR mRNA expression was dramatically increased with diabetes and, moreover, was not normalized by insulin. No differences in GR mRNA were detected between normal and STZ-diabetic rats. However, insulin treatment increased GR mRNA levels in the paraventricular nucleus and pituitary. We postulate that, in STZ-diabetes: 1) increased HPA activity is caused by increased central drive at and/or above the level of the paraventricular nucleus and is associated with decreased epinephrine; and 2) normalized pituitary-adrenal activity with insulin may be caused by the compensatory increase in GR mRNA allowing glucocorticoid-mediated suppression of ACTH secretion despite the residual increase in central HPA activity. Thus, insulin apparently restored HPA activity at and below the pituitary but, surprisingly, not above it.

Animals↗

The use of vena caval filters.

Deep vein thrombosis with pulmonary embolus is a frequent event, which is usually treated by anticoagulant drug therapy alone. Caval filters tend to be used infrequently in most centres in the UK. This article intends to help hospital doctors make use of these devices appropriately.

Humans↗

Computed tomography 21 days after chemotherapy, three-dimensional estimates of metastatic volume and the need for surgery in patients with germ cell cancer.

OBJECTIVE: To assess whether the response visible on computed tomography (CT) 21 days after the first course of chemotherapy in patients with nonseminomatous germ cell tumour predicts the need for surgery and whether three-dimensional (3D) reconstruction adds to the diagnostic accuracy. PATIENTS AND METHODS: CT scans from 52 patients treated with cisplatin-based chemotherapy were assessed for tumour shrinkage by measuring the changes of a one-dimensional (1D) measurement of the maximum transverse diameter, and comparing CT scans before, 21 days after the first course and at the end of chemotherapy (1D method). In a subset of patients, using a special formula, the 1D-derived 2D and 3D shrinkage (2Dder and 3Dder) were compared with four other computed or calculated methods (1D, 2D, 3Dcalc, 3Dcomp). RESULTS: At day 21, in 32 of 52 patients (62%) there was < 50% tumour shrinkage using the 1D assessment; 21 of them (66%) needed surgery, compared with none of the 20 patients with > 50% tumour shrinkage by day 21 (chi2 = 22.83, P < 0.001). The 1D method showed significantly less shrinkage than all the other methods but when this was used to derive a 3D shrinkage, assuming the mass to be spherical (3Dder), it was not statistically different from that of 3Dcomp. CONCLUSIONS: The assessment of the response from 1D CT scan estimates 21 days after initiating chemotherapy identifies a subgroup of patients who have a high probability of needing surgery. Although expected to be more accurate, the 3Dcomp estimate of tumour shrinkage was no better than the 3Dder estimate.

Adult↗

Effect of JTT-501 on net hepatic glucose balance and peripheral glucose uptake in alloxan-induced diabetic dogs.

JTT-501, a new insulin sensitizer, improves peripheral glucose uptake in insulin-resistant animals such as KK-Ay mice and Zucker fatty rats. However, the effect of JTT-501 on hepatic glucose metabolism has not been addressed. To investigate this effect, experiments were performed on 6 alloxan-diabetic dogs. Three experiments were conducted for each dog: the treatment experiment, which followed a 10-day oral treatment with JTT-501 30 mg x kg(-1) x d(-1), and 2 control experiments 2 weeks before and 2 weeks after the treatment experiment. A hyperinsulinemic-hyperglycemic clamp was performed with the tracer dilution method (intraportal insulin infusion rate, 18 pmol x kg(-1) x min(-1)). Arterial hyperglycemia (approximately 10 mmol/L) was maintained by adjusting the peripheral glucose infusion rate. After a 45-minute basal period (period I), portal glucose infusion (22.2 micromol x kg(-1)min(-1)) was administered for 120 minutes (period II). This was followed by a 90-minutes recovery period (period III). JTT-501 increased insulin-stimulated glucose utilization (P < .05) and enhanced insulin-mediated suppression of glucose production (P < .05) in periods I and III. Net hepatic glucose balance (NHGB) determined by the arterial-venous (A-V) difference method was increased by JTT-501 in period II (P < .01). We conclude that JTT-501 enhances both hepatic and peripheral insulin sensitivity and therefore may have important therapeutic effects in type 2 diabetes.

Alloxan↗

Radiography versus spiral CT in the evaluation of cervicothoracic junction injuries in polytrauma patients who have undergone intubation.

A prospective study was performed over a 1-year period in patients who had sustained blunt trauma, mostly in motor vehicle accidents. All 73 patients (56 male and 17 female; age range, 2-94 years; mean age, 35.2 years) in the study had undergone intubation and ventilation at the trauma site (mean Glasgow Coma Score, 9.9 [range, 3-15]; mean Injury Severity Score, 30.4 [range, 8-75]) and subsequently underwent three-view radiography of the cervical spine and thin-section spiral computed tomography (CT) of the cervicothoracic junction. Spinal fractures were detected in 20 patients and involved the cervicothoracic junction region in 12 cases. In all 12 patients, the fractures were visualized at CT, whereas in seven of 12 patients, conventional radiography failed to demonstrate injuries (transverse process fracture of T1 [n = 1], pedicle and vertebral body fracture of C7 [n = 1], fractures of the first and second ribs [n = 5]). Thus, routine CT of the cervicothoracic junction in a highly select group of severely injured patients helped detect occult fracture in seven of 73 patients (10%); however, most of these fractures were not clinically significant. Larger studies involving a high-risk patient population are needed to confirm these findings.

Accidents, Traffic↗

Comparison of patient-controlled sedation with propofol and alfentanil for third molar surgery--preliminary results of a pilot study.

Propofol and alfentanil are commonly used for sedation and pain control. A preliminary study to compare the usefulness of these drugs was carried out in ten healthy patients requiring bilateral wisdom tooth surgery. The operations were done in two appointments with the patient receiving a different drug on each occasion. Anxiety levels were recorded on visual analogue scales pre and post-operatively. Both agents caused a decrease in anxiety scores, with propofol causing a more significant reduction. Vomiting and nausea with alfentanil was noted in three patients. Propofol also had an amnesic effect which alfentanil did not have. In conclusion, propofol would appear to be the drug of choice within the limitations of this pilot study.

Adolescent↗

Pseudosubluxation of C2 on C3 in polytraumatized children--prevalence and significance.

AIM: Pseudosubluxation of C2 on C3 is a recognized physiological variant in the upper cervical spine radiographs of normal children. The aim of this study was to determine the prevalence of this variant in children admitted with serious polytrauma, and to explore its significance in this setting. PATIENTS AND METHODS: A retrospective review was performed of 138 patients under 16 years of age admitted with polytrauma via The Helicopter Emergency Medical Service. All patients wore hard collars and underwent immediate horizontal beam lateral cervical spine radiography. Normal and C2/C3 pseudosubluxation groups were defined using standard criteria. The two groups were compared in terms of age, presence of an endotracheal tube, injury severity, and outcome. RESULTS: There were 108 (78.3%) children in the normal group and 30 (21.7%) in the C2/C3 pseudosubluxation group. No significant differences in sex ratio, intubation status, injury severity, or outcome were found. Patients in the pseudosubluxation group were significantly younger. CONCLUSION: In paediatric polytrauma it is essential to establish the integrity of the cervical spine promptly as this will deter unnecessary further imaging and investigation. In our study 21.7% of cases had C2/C3 pseudosubluxation on admission radiographs. We have shown that C2/C3 pseudosubluxation has no significant association with intubation status, injury severity, or outcome. We conclude that C2/C3 pseudosubluxation can be considered a benign variant even in the setting of polytrauma.

Adolescent↗

Untreated chronic lymphocytic leukemia concurrent with or followed by acute myelogenous leukemia or myelodysplastic syndrome. A report of five cases and review of the literature.

Although it has been known that patients with chronic lymphocytic leukemia (CLL) have a higher frequency of second malignant neoplasms, the development of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in these patients is extremely rare. Most reported cases have been therapy-related. In this article, we report the clinical and immunophenotypic features of 5 cases of untreated CLL concurrent with or followed by the development of AML or MDS. All 5 patients were men, with ages ranging from 57 to 87 years (mean, 73.8 years). Four patients had AML and 1 patient had refractory anemia with ringed sideroblasts. In the 4 cases of AML and CLL, 2 distinct cell populations (i.e., myeloblasts and lymphocytes) were identified morphologically and/or immunophenotypically. Our findings support that this rare concurrence of AML or MDS and untreated CLL may represent 2 separate disease processes.

Aged↗

A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice.

A conventional view of the pathogenesis of systemic lupus erythematosus has emerged. The role of B cells is to secrete pathogenic autoantibodies, while the role of T cells is to provide help for autoantibody-producing B cells. A problem with this view is that spontaneous T cell activation as well as T cell infiltration of organs such as kidney and skin are prominent features in systemic lupus erythematosus patients and murine models of lupus. The identification of T cell infiltrates, in particular, suggests that autoantibody-mediated damage may be only part of the story and that T cells could also play a primary role in immune-mediated pathology. To test the role of B cells directly, we previously generated autoimmune-prone MRL-lpr/lpr mice that lack B cells. The complete absence of T cell infiltrates in these mice was surprising, and it prompted us to examine whether a key role of B cells in disease evolution is to prime autoreactive T cells. Here we demonstrate, by comparing B cell-deficient and control mice, that the expansion of activated and memory T cells in the MRL-lpr/lpr mouse is indeed highly dependent on B cells. These results suggest a novel role for B cells in autoimmune disregulation.

Age Factors↗

Tuberculosis of the mandible in a child.

The incidence of notification of tuberculosis is increasing in the developed world. The disease has a variable mode of presentation and therefore diagnosis is not easy. We present an unusual case of tuberculosis involving the ramus of the mandible in a six-year-old boy and outline its management.

Child↗

Potential of limited day 21 post-chemotherapy CT scan in predicting need for post-chemotherapy surgery in nonseminomatous testicular germ cell cancer.

UNLABELLED: Nonseminomatous germ cell cancers (NSGCC) have a varied response to chemotherapy, some melting away with resultant cure, some have tumour stem cell necrosis and residual benign disease whilst others are resistant to treatment. The latter two require surgical excision in order to identify those needing high intensity chemotherapy. OBJECTIVE: The aim of this study was to investigate whether it was possible to give an earlier prediction of need for surgery after chemotherapy on the basis of a limited CT scan performed after the first course. MATERIALS AND METHODS: Twenty-three patients with metastatic NSGCC undergoing induction chemotherapy were studied. The site of the maximum disease was noted before treatment and only this area was rescanned at day 21. The change in disease bulk, measured as maximum transverse diameter (MTD), was compared with appearances on a CT scan immediately after chemotherapy and post-treatment response. RESULTS: Of those patients showing a poor response on the day 21 scan (i.e. no change, or less than 50% reduction in MTD), 70% required early surgical excision of residual disease, while none of the good responders (i.e. greater than 50% reduction in MTD), required immediate surgery (p < 0.001). CONCLUSION: It is concluded that a limited day 21 CT scan may represent an independent predictor of good and poor response to chemotherapy, thus enabling reduction in chemotherapy and its toxicity in good responders and early identification of those who may need surgical excision, thereby permitting easier scheduling of these often difficult surgical procedures.

Adult↗